ICU · Respiratory
Severe asthma: phenotypes, biologics, and ICU management update
Also known as Severe asthma · Status asthmaticus · Asthma biologics · Type 2 asthma · Eosinophilic asthma · Omalizumab · Mepolizumab · Benralizumab · Dupilumab · Tezepelumab · TSLP inhibitor · Periostin · Eosinophilic asthma · Neutrophilic asthma
Severe asthma: asthma requiring high-dose inhaled corticosteroids + second controller (or systemic steroids) to maintain control, or remaining uncontrolled despite these. PHENOTYPES: (1) Type 2 (T2) — high eosinophils/FeNO, allergic, good steroid response. (2) Non-T2 — neutrophilic, paucigranulocytic, poor steroid response. BIOLOGICS for severe T2 asthma: omalizumab (anti-IgE), mepolizumab/benralizumab (anti-IL-5), dupilumab (anti-IL-4Rα). ICU management of acute severe asthma: oxygen, SABA/SAMA, systemic steroids, magnesium, may need ventilation (permissive hypercapnia, ketamine). NEW: biologics reduce exacerbations (50-70%) but are NOT for acute attacks (prophylactic only).
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Red flags
- Acute severe asthma with silent chest, exhaustion, altered consciousness — imminent respiratory arrest, prepare for intubation
- Normocapnia or hypercapnia in asthma = fatigue/impending arrest (should be hypocapnic)
- Non-T2 (neutrophilic) asthma — biologic targets don't work, steroids less effective
Meet the patient
A 42-year-old with childhood asthma, eczema, and allergic rhinitis has needed four corticosteroid bursts and one ICU admission despite high-dose inhaled therapy. Blood eosinophils are 480 cells per microlitre, FeNO is 62 ppb, total IgE is 320 IU/mL, and perennial allergen testing is positive.[1]
She appears eligible for several biologics. The consultant question is therefore not which drug is newest? It is which inflammatory pathway is active, which clinical problem matters most, and how will we prove response?[1]
References11ShowHide
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- [3]Pavord ID, Korn S, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet, 2012.PMID 22901886
- [4]Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta(2)-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet, 2016.PMID 27609408
- [5]Castro M, Corren J, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med, 2018.PMID 29782217
- [6]Menzies-Gow A, Corren J, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med, 2021.PMID 33979488
- [7]Higgins JC The crashing asthmatic. Am Fam Physician, 2003.PMID 12643359
- [8]Wong JJ, Lee JH, et al. A review of the use of adjunctive therapies in severe acute asthma exacerbation in critically ill children. Expert Rev Respir Med, 2014.PMID 24993063
- [9]Burburan SM, Xisto DG, et al. Anaesthetic management in asthma. Minerva Anestesiol, 2007.PMID 17115010
- [10]Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial Lancet, 2017.PMID 28687413
- [11]Castro M, Rubin AS, Laviolette M, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial Am J Respir Crit Care Med, 2010.PMID 19815809